RTN1 is an endoplasmic reticulum-associated protein that has initially been identified in neuronal tissues. Here we show that the main isoform RTN1A is a marker for dendritic cells. In the skin HLA-DR+CD1ahighCD207+CD11cweak Langerhans cells were the only cells in the epidermis and HLA-DR+CD11c+ dendritic cells were the main cells in the dermis expressing this protein. RTN1A+ dendritic cells were also demonstrated in gingiva, trachea, tonsil, thymus and peripheral blood. During differentiation of MUTZ-3 cells into Langerhans cells, expression of RTN1A mRNA and protein preceded established Langerhans cell markers CD1a and CD207, and RTN1A protein partially co-localized with the endoplasmic reticulum marker protein disulfide isomerase. In line with this observation, we found that RTN1A was expressed by around 80% of Langerhans cell precursors in human embryonic skin. Our findings show that RTN1A is a marker for cells of the dendritic lineage including Langerhans cells and dermal dendritic cells. This unexpected finding will serve as a starting point for the elucidation of the, as yet, elusive functional roles of RTN1A in both the immune and the nervous system.